EP2033620A1 - Formulation of natural triterpenes and biophenols obtained from the genus olea in liposomes - Google Patents
Formulation of natural triterpenes and biophenols obtained from the genus olea in liposomes Download PDFInfo
- Publication number
- EP2033620A1 EP2033620A1 EP07788547A EP07788547A EP2033620A1 EP 2033620 A1 EP2033620 A1 EP 2033620A1 EP 07788547 A EP07788547 A EP 07788547A EP 07788547 A EP07788547 A EP 07788547A EP 2033620 A1 EP2033620 A1 EP 2033620A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- biophenols
- liposomes
- natural
- formulation
- triterpenes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000203 mixture Substances 0.000 title claims abstract description 47
- 239000002502 liposome Substances 0.000 title claims abstract description 38
- 150000003648 triterpenes Chemical class 0.000 title claims abstract description 32
- 241000795633 Olea <sea slug> Species 0.000 title claims abstract description 13
- 238000009472 formulation Methods 0.000 title claims description 20
- JUUBCHWRXWPFFH-UHFFFAOYSA-N Hydroxytyrosol Chemical compound OCCC1=CC=C(O)C(O)=C1 JUUBCHWRXWPFFH-UHFFFAOYSA-N 0.000 claims abstract description 52
- YCCILVSKPBXVIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)ethanol Chemical compound OCCC1=CC=C(O)C=C1 YCCILVSKPBXVIP-UHFFFAOYSA-N 0.000 claims abstract description 34
- MDZKJHQSJHYOHJ-LLICELPBSA-N maslinic acid Chemical compound C1[C@@H](O)[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MDZKJHQSJHYOHJ-LLICELPBSA-N 0.000 claims abstract description 28
- 235000003248 hydroxytyrosol Nutrition 0.000 claims abstract description 26
- 229940095066 hydroxytyrosol Drugs 0.000 claims abstract description 26
- MDZKJHQSJHYOHJ-UHFFFAOYSA-N crataegolic acid Natural products C1C(O)C(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MDZKJHQSJHYOHJ-UHFFFAOYSA-N 0.000 claims abstract description 24
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 claims abstract description 21
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 claims abstract description 21
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 claims abstract description 21
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 claims abstract description 21
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229940100243 oleanolic acid Drugs 0.000 claims abstract description 20
- DBLDQZASZZMNSL-QMMMGPOBSA-N L-tyrosinol Natural products OC[C@@H](N)CC1=CC=C(O)C=C1 DBLDQZASZZMNSL-QMMMGPOBSA-N 0.000 claims abstract description 17
- 235000004330 tyrosol Nutrition 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 14
- 239000012153 distilled water Substances 0.000 claims description 9
- 239000012141 concentrate Substances 0.000 claims description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 7
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 7
- 229960000541 cetyl alcohol Drugs 0.000 claims description 7
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 7
- 241000894007 species Species 0.000 claims description 7
- 229940045860 white wax Drugs 0.000 claims description 7
- 235000013311 vegetables Nutrition 0.000 claims description 5
- 239000002699 waste material Substances 0.000 claims description 5
- 235000013399 edible fruits Nutrition 0.000 claims description 3
- 229930014626 natural product Natural products 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 description 30
- 230000008569 process Effects 0.000 description 23
- 240000007817 Olea europaea Species 0.000 description 17
- 238000004519 manufacturing process Methods 0.000 description 13
- 239000002253 acid Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 239000006227 byproduct Substances 0.000 description 9
- 239000006071 cream Substances 0.000 description 8
- 238000003801 milling Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- GXWUEMSASMVWKO-GNLHUFSQSA-N (4as,6ar,6as,6br,10s,12ar,14br)-10-[(2s,3r,4s,5s)-4,5-dihydroxy-3-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid Chemical compound O([C@@H]1[C@@H](O)[C@@H](O)CO[C@H]1O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CCC2C1(C)C)C)(C)CC[C@]1(CCC(C[C@@H]14)(C)C)C(O)=O)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GXWUEMSASMVWKO-GNLHUFSQSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 150000003904 phospholipids Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 241000700605 Viruses Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 241000207836 Olea <angiosperm> Species 0.000 description 3
- 235000002725 Olea europaea Nutrition 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000223935 Cryptosporidium Species 0.000 description 2
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000036436 anti-hiv Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000002443 hepatoprotective effect Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 2
- 230000003859 lipid peroxidation Effects 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 208000029483 Acquired immunodeficiency Diseases 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- YKOPWPOFWMYZJZ-FMMUPTMQSA-N Echinocystic acid Natural products C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)C[C@H](O)[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C YKOPWPOFWMYZJZ-FMMUPTMQSA-N 0.000 description 1
- YKOPWPOFWMYZJZ-UHFFFAOYSA-N Echinocystsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CC(O)C5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C YKOPWPOFWMYZJZ-UHFFFAOYSA-N 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- 235000009709 Geum japonicum Nutrition 0.000 description 1
- 241001618015 Geum japonicum Species 0.000 description 1
- 241000931164 Gleditsia japonica Species 0.000 description 1
- 241000931142 Gymnocladus chinensis Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001327682 Oncorhynchus mykiss irideus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 235000000204 Solanum lycocarpum Nutrition 0.000 description 1
- 241000047047 Solanum lycocarpum Species 0.000 description 1
- 241000830536 Tripterygium wilfordii Species 0.000 description 1
- -1 Triterpene Acids Chemical class 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 241001135917 Vitellaria paradoxa Species 0.000 description 1
- 239000004015 abortifacient agent Substances 0.000 description 1
- 231100000641 abortifacient agent Toxicity 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000000170 anti-cariogenic effect Effects 0.000 description 1
- 230000003509 anti-fertility effect Effects 0.000 description 1
- 230000001929 anti-hepatotoxic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000010335 hydrothermal treatment Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000003808 methanol extraction Methods 0.000 description 1
- MCHWKJRTMPIHRA-UHFFFAOYSA-N n-(pyrrolidin-2-ylmethyl)aniline Chemical compound C1CCNC1CNC1=CC=CC=C1 MCHWKJRTMPIHRA-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000037307 sensitive skin Effects 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 229940057910 shea butter Drugs 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 235000015398 thunder god vine Nutrition 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 150000008130 triterpenoid saponins Chemical class 0.000 description 1
- 230000003191 uterotonic effect Effects 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention consists of a formulation of natural triterpenes and biophenols obtained from the genus Olea in liposomes, specifically of triterpenes from the group comprised of maslinic acid and/or its salts, oleanolic acid and/or its salts, tyrosol and hydroxytyrosol in liposomes.
- Oleanolic acid (3-beta-hydroxy-28-carboxy-oleanene) is a triterpenic acid ubiquitously distributed within the plant kingdom.
- oleanolic acid in addition to echinocystic acid (16-hydroxy-oleanolic) have been found to have inhibiting effects against the replication of HIV in H-9 cells with EC50 values of 2.3 mM
- Anti-AIDS agents 21. Triterpenoid saponins as anti-HIV principles from fruits of Gleditsia japonica and Gymnocladus chinensis, and a structure-activity correlation, Konoshima, Takao; Yasuda, Ichiro; Kashiwada, Yoshiki; Cosentino, L. Mark; Lee,Kuo-Hsiung, J. Nat. Prod., 58(9), 1372-7, (1995 )).
- Leukotriene D4 antagonists Leukotriene D4 antagonists in Tripterygium wilfordii, Morota, Takashi; Saitoh, Kazuko; Maruno, Masao; Yang, Chun-Xin; Qin, Wan-Zhang; Yang, Bing-Hui, Nat. Med., 49(4), 468-71 (1995 )).
- oleanolic acid as a vasodilator and restorer agent for endothelial dysfunction
- Cosmetic and dermopharmaceutical compositions for skin prone to acne WO2002FR03344 20021001
- Cosmetic composition for care of sensitive skin includes oleanolic acid or vegetable extract rich in oleanolic acid, and at least one other vegetable extract chosen from shea-butter flower and solanum lycocarpum ( FR20000008758 20000705 ); Process for preparing food products fortified with oleanolic acid ( US19990468637 19991222 ); Oleanolic acid-based anti-pruritus agent ( JP19970183075 19970623 ); Angiogenesis inhibitor composition comprising oleanolic acid ( KR19920021117 19921111 ).
- HAV-1 Aids virus protease
- HAV-1 Anti-HIV Triterpene Acids from Geum japonicum, Xu, H.X.; Zeng, F.; Wan, M.; Sim, Keng-Yeow J. Nat. Prod., 59(7), 643-645 (1996 )
- maslinic acid acts as an active component: Antitumor agent US20030355201 20030131 ; Apoptosis inductor ( W02002JP13663 20021226 ); Antiobestic foods and drinks ( WO2002JP11608 20021107 ); External agent for the skin and whitening agent ( US20020259323 20020930 ); Antiobesity drugs and materials thereof ( W02002JP07709 20020730 ); Drugs for vascular lesion ( W02002JP03189 20020329 ); Antitumor food or beverage ( W02001 J P 11374 20011225 ).
- This process which consists of the concentration of vegetation water, de-oiled from the extract, subsequent extraction with ethyl acetate and separation of the contents of this extract by means of chromatography-based processes allowed the high-purity isolation of the biophenols present in this extract (fundamentally tyrosol and hydroxytyrosol).
- Hydroxytyrosol concentrates are marketed with the names Hidrox® (Internet Address http://www.creagri.com/hidrox/proprietary.html) and related products "Method of obtaining a hydroxytyrosol-rich composition from vegetation water” ( US Patent 6416808 ) (Internet Address http://www.patentstorm.us/patents/6416808.html).
- Hytolive® Internet Address http://www.hytolive.com
- Olidrox® Internet Address http://www.cotecportugal.pt/cotec/images/pdf/Olidrox.pdf
- the line of action consists of a hydrothermal treatment and provoking a prior hydrolysis of various natural components that structurally contain tyrosol and hydroxytyrosol, with or without catalysis, performing filtration processes with membranes and subsequently isolating these phenols in a greater or lesser degree of purity by separation with various types of exchange resins.
- a large quantity of processes have been developed for the isolation of antioxidants from olive leaves (for example, European Patent EP1389465 ).
- the University of Granada has an industrial patent ( P9601652 , W098/04331 , Process for the industrial use of 3beta-hydroxy-olean-12-en-28-oic (oleanolic) acid and 2alpha,3beta-dihydroxy-olean-12-en-28-oic (maslinic) acid contained in the olive milling by-products), which allows the industrial production of these two acids, separately and in a high degree of purity, from solid by-products of industrial olive milling, by any of the currently used processes (presses, continuous in the three-phase and the so-called two-phase), which represents an attainable and practically inexhaustible source thereof.
- liposomes are spherical vesicles obtained from the interaction of phospholipids. Their formation is not spontaneous but rather induced by the presence of water.
- Phospholipids are antipathic molecules, that is, they are comprised of two different parts, one of which is hydrophilic and the other hydrophobic. This characteristic of phospholipids is the cause, when dispersed in water, of the molecules becoming oriented in space, forming micellar structures known as liposomes. Liposomes are characterised by being spherical structures that contain the aqueous medium used for their dispersion.
- Liposomes were initially used as cellular membrane models for biophysical studies due to their structural similarity to the cytoplasmatic membranes of most of the cells of living organisms. It was precisely this similarity which gave rise to the idea of their use as a method for transporting substances in topical and parenteral administration.
- the separation process established is totally physical and extremely effective, allowing the two products to be isolated in the desired proportions from complex original mixtures. This allows us to obtain natural oleanolic and maslinic acid by recovering these from the previously milled olive; due to the extremely hydrophobic nature of these triterpenes, they are immediately associated to the hydrophobic part of the phospholipids, due to which their inclusion is simple and immediate.
- the amount of substance to be added is limited by the amount of phospholipids present in the liposomic dispersion.
- spherical liposomes (not laminated), which are readily available on the market, and add the biophenols dissolved in a minimum amount of water.
- This hydrophilic composition is added, preferably hot and by stirring vigorously, to a hydrophobic base already containing the triterpenes.
- This preparation method accepts from 0.0001% to 20% in weight of final product of the natural biophenols and triterpenes in liposomes.
- biophenols and triterpenes obtained from the genus Olea in liposomes, which is composed of at least one of the triterpenes of the group consisting of maslinic acid and oleanolic acid and/or their salts, and at least one of the biophenols of the group consisting of hydroxytyrosol and/or tyrosol and by liposomes.
- the biophenols and triterpenes are added to the liposomes as natural products contained in species, subspecies or varieties of the genus Olea that contain at least one of the triterpenes and/or biophenols in an amount greater than 0.001 % of the dry vegetable matter, or the triterpenes and/or biophenols are extracted from the fruit-mill waste of species, subspecies or varieties of the genus Olea that contain at least one of the triterpenes and/or biophenols in an amount greater than 0.001 % of the dry waste.
- the triterpenes and/or biophenols used are in the form of concentrate or extract of species, subspecies or varieties of the genus Olea, and in solid or liquid form, and that at least one of the selected triterpenes and/or biophenols is present in the amount of between 10% and 95% of the total mixture of triterpenes and/or biophenols respectively.
- the formulation of the invention may have the following composition: mg / 100 g Maslinic Acid 0-20000 Oleanolic Acid 0-10000 Tyrosol 1-20000 Hydroxytyrosol 1-10000 Propylene glycol 0-50000 Liposomes 100-99000 Cetyl alcohol 0-50000 White wax 0-50000 Sodium lauryl sulphate 0-50000 Distilled water q.s. 100 g
- the formulation has the following formulation: g / 100 g Maslinic Acid 1.7 Oleanolic Acid 0.28 Tyrosol 0.18 Hydroxytyrosol 0.02 Propylene glycol 10 Liposomes 36 Cetyl alcohol 15 White wax 1 Sodium lauryl sulphate 2 Distilled water q.s. 100 g
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200601435A ES2286953B1 (es) | 2006-05-18 | 2006-05-18 | Formulacion de triterpenos naturales y biofenoles obtenidos del genero olea en liposomas. |
| PCT/ES2007/000288 WO2007135210A1 (es) | 2006-05-18 | 2007-05-18 | Formulación de triterpenos naturales y biofenoles obtenidos del genero olea en liposomas |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP2033620A1 true EP2033620A1 (en) | 2009-03-11 |
Family
ID=38698487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP07788547A Withdrawn EP2033620A1 (en) | 2006-05-18 | 2007-05-18 | Formulation of natural triterpenes and biophenols obtained from the genus olea in liposomes |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20100055163A1 (es) |
| EP (1) | EP2033620A1 (es) |
| ES (1) | ES2286953B1 (es) |
| WO (1) | WO2007135210A1 (es) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2813221A1 (en) | 2013-06-13 | 2014-12-17 | Natac Biotech, S.L. | Combination of pentacyclic triterpenes and hydroxytyrosol and derivatives thereof |
| EP3999023A4 (en) * | 2019-08-23 | 2023-07-05 | Colgate-Palmolive Company | METHOD FOR INCORPORATION OF OLEANOLIC ACID INTO ORAL CARE COMPOSITIONS AND ORAL CARE COMPOSITIONS BASED THEREOF |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2782441A1 (en) * | 2009-12-01 | 2011-06-09 | Seprox Biotech, S.L. | Topical use of hydroxytyrosol and derivatives for the prevention of hiv infection |
| KR101821207B1 (ko) * | 2010-11-22 | 2018-01-24 | (주)아모레퍼시픽 | 올레아놀릭산을 함유하는 화장료 조성물 |
| CN103694302B (zh) * | 2013-12-04 | 2016-03-30 | 中国科学院华南植物园 | 2α,3β-二羟基-30-齐墩果-12,20(29)-二烯-28-酸的制备方法和在制备抗肿瘤药物中的应用 |
| ES2756898B2 (es) * | 2018-10-26 | 2021-11-26 | E Grau Active Cosmetics S L U | Un concentrado a base de aceite de oliva y un preparado de aplicación tópica para el cuidado de la piel que comprende dicho concentrado |
| EP4438030A1 (en) * | 2023-03-21 | 2024-10-02 | E Grau Active Cosmetics, S.L.U. | Ternary anti-spot combination to lighten skin |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES211498A1 (es) | 1952-11-07 | 1955-01-16 | Ruthner Othmar | UN DISPOSITIVO PARA DECAPAR CINTAS DE HIERRO Y METáLICAS |
| FR2676911B1 (fr) | 1991-05-30 | 1998-03-06 | Psi Ste Civile Particuliere | Dispositif de stabilisation intervertebrale a amortisseurs. |
| ES2111498B1 (es) | 1996-07-25 | 1998-09-01 | Univ Granada | Procedimiento de aprovechamiento industrial de los acidos oleanolico y maslinico contenidos en los subproductos de la molturacion de la aceituna. |
| IT1298283B1 (it) | 1998-02-19 | 1999-12-20 | B & T S R L | Uso dell'estratto delle foglie di olea europea come antiradicalico |
| US6165475A (en) | 1998-07-23 | 2000-12-26 | Creagri, Inc. | Water-soluble extract from olives |
| MXPA01000776A (es) | 1998-07-23 | 2002-04-08 | Creagri Inc | Extracto de oliva soluble en agua. |
| CA2419041A1 (en) * | 2000-08-08 | 2003-02-10 | The Nisshin Oillio, Ltd. | Method for the preparation of oleanolic acid and/or maslinic acid |
| AU8858001A (en) | 2000-09-01 | 2002-03-13 | Creagri Inc | Method of obtaining a hydroxytyrosol-rich composition from vegetation water |
| FR2830195B1 (fr) * | 2001-10-03 | 2004-10-22 | Sederma Sa | Compositions cosmetiques et dermopharmaceutiques pour les peaux a tendance acneique |
| ES2193874B1 (es) * | 2002-04-03 | 2005-03-01 | Puleva Biotech, S.A. | Compuestos naturales y derivados de estos para la prevencion y el tratamiento de enfermedades cardiovasculares, hepaticas, renales y cosmeticas. |
| KR100489701B1 (ko) * | 2002-10-09 | 2005-05-16 | 주식회사 태평양 | 고농도의 트리터페노이드를 함유하는 미소화 리포좀 및 그제조방법 |
| EP1765463B1 (en) * | 2004-07-01 | 2014-07-30 | E-L Management Corp. | Cosmetic compositions and methods containing a tanning agent and liposome-enscapsulated ursolic acid |
| ES2267402B1 (es) * | 2005-08-17 | 2008-03-16 | Universidad De Granada | Formulacion de triterpenos naturales obtenidos del genero olea en liposomas. |
-
2006
- 2006-05-18 ES ES200601435A patent/ES2286953B1/es active Active
-
2007
- 2007-05-18 US US12/301,365 patent/US20100055163A1/en not_active Abandoned
- 2007-05-18 EP EP07788547A patent/EP2033620A1/en not_active Withdrawn
- 2007-05-18 WO PCT/ES2007/000288 patent/WO2007135210A1/es active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2007135210A1 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2813221A1 (en) | 2013-06-13 | 2014-12-17 | Natac Biotech, S.L. | Combination of pentacyclic triterpenes and hydroxytyrosol and derivatives thereof |
| JP2016521717A (ja) * | 2013-06-13 | 2016-07-25 | ナタク バイオテク、エセ． エレＮａｔａｃ Ｂｉｏｔｅｃｈ，Ｓ．Ｌ | ５環性トリテルペンとヒドロキシチロソール及びその誘導体との組み合わせ |
| US10376529B2 (en) | 2013-06-13 | 2019-08-13 | Natac Biotech, S.L. | Combination of pentacyclic triterpenes and hydroxytyrosol and derivatives thereof |
| EP3999023A4 (en) * | 2019-08-23 | 2023-07-05 | Colgate-Palmolive Company | METHOD FOR INCORPORATION OF OLEANOLIC ACID INTO ORAL CARE COMPOSITIONS AND ORAL CARE COMPOSITIONS BASED THEREOF |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2286953B1 (es) | 2008-12-16 |
| WO2007135210A1 (es) | 2007-11-29 |
| US20100055163A1 (en) | 2010-03-04 |
| ES2286953A1 (es) | 2007-12-01 |
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